Capturing Acute and Subchronic Myocardial Infarct by MRI Rotating Frame Relaxation Times in Mice In and Ex Vivo

Abstract

Abstract

Cardiovascular diseases are the leading cause of death worldwide due to population growth and aging. Myocardial infarct is one of the most crucial cardiovascular diseases. Acute myocardial infarct is conventionally imaged with magnetic resonance imaging (MRI) with T2 mapping due to its sensitivity related to the correlation times of edema and free water molecules. Chronic myocardial infarction, which contains fibrosis and scar tissue, is conventionally imaged with MRI by using contrast agents since contrast agent washout from fibrosis and scar tissue is delayed compared to myocardium. Rotating frame relaxation times T1ρ and T2ρ mappings were developed to provide robust measurements with relatively wide B1 and B0 ranges for these quantities. Since rotating frame methods are sensitive to slow molecular motions, these methods owe potential to characterize both acute and chronic myocardial infarctions. In this study, rotating frame relaxation time mappings were applied to image acute (2 h) and subchronic (7 days after occlusion) myocardial infarcts in in vivo and ex vivo mouse models without using contrast agents. The in vivo imaging protocol contained adiabatic T1ρ and adiabatic T2ρ, both with hyperbolic secant (HS) 1 and 4 pulses, continuous wave T1ρ and conventional T2, together with cine imaging. Mice were imaged 2 h and 7 days after myocardial infarction. Mice were sacrificed at the 2-h or 7-day time point. Ex vivo measurements contained adiabatic T1ρ and adiabatic T2ρ with HS1 and HS4 pulses, continuous wave T1ρ, T1, and T2. After MRI studies, mouse hearts were fixed, and myocardial infarcts were verified using dystrophin and hematoxylin and eosin histology stainings. A clear difference between infarcted and normal myocardium was visible at the 2-h time point in rotating frame relaxation time mapping. Relative relaxation time difference in adiabatic T2ρ with HS4 pulse showed the significant differences between MI and control hearts in vivo. In addition, the results of adiabatic T1ρ with both HS1 and HS4 pulses and continuous wave T1ρ measurements showed significant differences between MI and control hearts at both time points in both in vivo and ex vivo measurements. This study shows that rotating frame relaxation time mappings have the potential to be noninvasive MR diagnostic markers for acute and subchronic myocardial infarcts.